Endogenous Substances Single Protein Analysis 9411 Hormones and Growth Factors

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A variety of hormones have been measured in NAF, including estrogens, androgens, progesterone, dehydroepiandrosterone sulfate, prolactin, growth hormone, and the growth factors epidermal growth factor, transforming growth factor-a, vascular endothelial growth factor, and basic fibroblast growth factor (Chatterton et al., 2004; Hsiung et al., 2002; Petrakis, 1989; Sauter et al., 2002b). Elevated levels of estrogens, cholesterol, and cholesterol epoxides have been suggested to have etiologic significance in breast disease (Petrakis, 1993).

Levels of a number of these factors have been compared to disease risk. With the exception of recent parity, no relation was found between levels of estrogen in NAF and breast cancer risk. Higher levels of estradiol and estrone were found in the NAF of women with benign breast disease than in controls (Ernster et al., 1987). There is a decrease in estradiol and estrone levels in NAF following pregnancy or lactation that persists for several years before returning to prepregnancy levels

(Petrakis et al., 1987). This period of decreased estrogen exposure of the breast epithelium of postpartum women has been suggested to partially explain the protective effect of early pregnancy.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are two of the most important angiogenic factors that stimulate tumor growth (Folkman and Klagsbrun, 1987; Folkman and Shing, 1992). A preliminary report that analyzed 10 patients with breast cancer and 10 controls found that bFGF levels in NAF were higher in women with breast cancer than in normal subjects (Liu et al., 2000). A larger study, which evaluated 143 NAF specimens (Hsiung et al., 2002), also found that mean NAF bFGF levels were significantly higher in women with breast cancer than in those without. VEGF levels in NAF were not associated with breast cancer. A logistic regression model including NAF levels of bFGF and clinical variables was 90% sensitive and 69% specific in predicting which women had breast cancer. Adding another biomarker linked to breast cancer, prostate-specific antigen (PSA), increased the sensitivity to 91% and the specificity to 83%.

Leptin is a hormone that plays a central role in food intake and energy expenditure (Macajova et al., 2004). Systemic levels of leptin are increased in obese individuals, and have been found to stimulate the growth of breast cancer cells in vitro. Leptin levels in NAF were more readily measured in post- than in premeno-pausal women and were significantly higher in postmenopausal women with a body mass index (BMI) < 25 (Sauter et al., 2004a). While NAF leptin levels were not associated with pre- or postmenopausal breast cancer, they were associated with premenopausal BMI.

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